Although schizophrenia is diagnosed on the basis of its phenomenological symptoms and longitudinal course, almost all schizophrenic patients demonstrate significant cognitive dysfunction. The relationship between cognitive deficits and the neuroanatomic dysfunction and symptoms of schizophrenia is not understood. Recently developed models of the relationship between brain function and cognition in human and nonhuman primates suggest that even the most basic cognitive functions are mediated by complex neural circuitry. The advent of these models, coupled with the inability of neuroanatomic localization models to account for the symptoms of schizophrenia, suggest that the cognitive deficits and symptoms of schizophrenia may be explained by dysfunctions in the neural circuitry of these patients. Project 1 will address the relationship between cognitive deficits and patterns of neuroanatomic activation in schizophrenia as assessed by PET. Project 2 will involve testing models of neural circuitry dysfunction in schizophrenia by analyzing PET data with confirmatory path analysis. These projects will be informed by laboratory work on the connectivity of human neural tissue, particularly the neural circuits connecting the prefrontal cortex with the thalamus and the hippocampus via the caudate nucleus, entorhinal cortex and parahippocampal gyrus. The final phase of the proposed research plan will build upon the skills acquired as part of the career development plan focusing on basic neuroscience and neural network modeling.